2p1l
From Proteopedia
Structure of the Bcl-XL:Beclin 1 complex
Structural highlights
Function[B2CL1_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.[1] [2] Isoform Bcl-X(S) promotes apoptosis.[3] [4] [BECN1_HUMAN] Plays a central role in autophagy. Required for the abcission step in cytokinesis. May play a role in antiviral host defense. Protects against infection by a neurovirulent strain of Sindbis virus.[5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBcl-2 family proteins are key regulators of apoptosis and have recently been shown to modulate autophagy. The tumor suppressor Beclin 1 has been proposed to coordinate both apoptosis and autophagy through direct interaction with anti-apoptotic family members Bcl-2 and/or Bcl-X(L). However, the molecular basis for this interaction remains enigmatic. Here we report that Beclin 1 contains a conserved BH3 domain, which is both necessary and sufficient for its interaction with Bcl-X(L). We also report the crystal structure of a Beclin BH3 peptide in complex with Bcl-X(L) at 2.5A resolution. Reminiscent of previously determined Bcl-X(L)-BH3 structures, the amphipathic BH3 helix of Beclin 1 bound to a conserved hydrophobic groove of Bcl-X(L). These results define Beclin 1 as a novel BH3-only protein, implying that Beclin 1 may have a direct role in initiating apoptotic signaling. We propose that this putative apoptotic function may be linked to the ability of Beclin 1 to suppress tumor formation in mammals. Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein.,Oberstein A, Jeffrey PD, Shi Y J Biol Chem. 2007 Apr 27;282(17):13123-32. Epub 2007 Mar 2. PMID:17337444[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Jeffrey, P D | Oberstein, A L | Shi, Y | Apoptosis | Autophagy | Bcl | Beclin | Bh3 domain
